Human Herpesvirus 6 ("HHV-6"), a beta herpesvirus first described by Salahuddin and colleagues in 1986, is present in a latent state in about ninety percent of the human population. During periods of active infection, however, the virus is associated with various clinical illnesses.
HHV-6 is genotypically and phenotypically subtyped into variant forms A and B ("HHV-6A" and "HHV-6B", respectively). HHV-6B is responsible for the majority of clinical illness associated with HHV-6 in humans. Much less is known about pathology of HHV-6A. HHV-6 is genetically distinct from the other herpesvirus, which include Herpes Simplex Virus-1, Herpes Simplex Virus-2, Cytomegalovirus, Epstein-Barr Virus and Varicella Zoster Virus.
HHV-6 is the clinical etiological agent of roseola infantum and exanthem subitum in children and is commonly associated with clinically significant bone marrow suppression in infants with primary HHV-6 infections. In adults, HHV-6 is causally associated with a wide spectrum of clinic illness, which can be fatal in at-risk immunocompromised or immunosuppressed populations. Notably, HHV-6 is prominent in patients having pneumonitis and encephalitis and in patients immunosuppressed following allogeneic bone marrow transplant (AlBMT) or solid organ transplant.
In AlBMT patients, HHV-6 associated bone marrow suppression (HBMS) correlates with direct viral infection of the bone marrow. Persistent infection by HHV-6 of bone marrow can cause chronic bone marrow suppression. In vitro experiments have both confirmed the bone marrow suppressive properties of HHV-6 and have shown that the suppression is mediated by cytokines or virus-produced soluble factors.
HHV-6 has also been suggested to be a co-factor in causation of HIV disease, and may be involved with febrile convulsions in children, multiple sclerosis, and chronic fatigue syndrome.
When HHV-6 is diagnosed promptly after infection, it can be treated effectively using available antiviral agents such as ganciclovir and foscarnet which suppress viral replication. Unfortunately, the art has been forced to rely upon one of three difficult, expensive and time consuming methods for diagnosing active HHV-6 infection.
The preferred available diagnostic method involves isolating the virus from cell culture after co-cultivating a patient sample with mitogen-stimulated umbilical cord lymphocytes for a period that can be as long as three weeks. This procedure is not routinely available in virology laboratories, and is too slow to be of practical use to clinicians.
Active HHV-6 infection can also be demonstrated using a polymerase chain reaction (PCR) protocol to detect HHV-6 viral DNA in an acellular specimen such as cerebro-spinal fluid or serum. This technique, too, is generally unavailable and expensive.
Finally, active HHV-6 infection is shown by positive immunohistochemical staining of a tissue biopsy or cytological preparation (e.g., BAL) using an antiserum or monoclonal antibody that reacts with late-appearing viral structural proteins. This third technique is highly specialized, is not routinely available in histology laboratories, and is less likely to detect early HHV-6 infections.
Since effective treatment depends upon early diagnosis of infection, an improved ability to facilitate early detection of HHV-6 is desired.